Selective aryl α-diimine/palladium-catalyzed bis-alkoxycarbonylation of olefins for the synthesis of substituted succinic diesters

Article abstract of DOI:10.1002/adsc.201400501

Aryl α-diimine derivatives have been used, for the first time, as efficient new ligands for the palladium-catalyzed oxidative bis-alkoxycarbonylation reaction of olefins. The most active catalyst was formed in situ from bis(9-anthryl)-2,3-dimethyl-1,4-dia

Full text of DOI:10.1002/adsc.201400501

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DOI: 10.1002/adsc.201400501
Selective Aryl a-Diimine/Palladium-Catalyzed Bis-Alkoxy-
carbonylation of Olefins for the Synthesis of Substituted
Succinic Diesters
Francesco Fini,a,* Michela Beltrani,a Raffaella Mancuso,b Bartolo Gabriele,b
and Carla Carfagnaa,*
a
Department of Biomolecular Sciences, University of Urbino, Piazza Rinascimento 6, 61029 Urbino (PU), Italy
Fax : (+39)-0722-303-306; phone: (+39)-0722-303-312; e-mail: fini_f@libero.it or carla.carfagna@uniurb.it
Department of Chemistry and Chemical Technologies, University of Calabria, Via P. Bucci 12/C, 87036 Arcavacata di
b
Rende (CS), Italy
Received: May 20, 2014; Revised: August 1, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400501.
Abstract: Aryl a-diimine derivatives have been used, carbon monoxide (CO) at 208C in the presence of p-
for the first time, as efficient new ligands for the pal- toluenesulphonic acid as additive and p-benzoqui-
ladium-catalyzed oxidative bis-alkoxycarbonylation none as oxidant]. The optimized conditions could be
reaction of olefins. The most active catalyst was successfully applied to both aromatic and aliphatic
formed in situ from bis(9-anthryl)-2,3-dimethyl-1,4- olefins, by using methanol, benzyl alcohol or isopro-
diazabutadiene and palladium(II) trifluoroacetate pyl alcohol as nucleophiles.
[Pd(TFA)2]. This catalytic system was able to selec-
tively convert olefins into succinic diesters in good Keywords: alkenes; aryl a-diimine ligands; carbony-
yields (up to 97%) and low catalyst loading (up to lation; oxidative carbonylation; palladium; succinic
0.5 mol%) under mild reaction conditions [4 bar of acid esters
Introduction
Heck,[3] a big leap was made by Chauvin et al. in
1990.[7h] By employing butyl nitrite as the oxidizing
Oxidative carbonylations are among the most impor- agent, they were able to increase the catalytic effi-
tant reactions in the field of palladium catalysis,[1] ciency up to 300 TON, under relatively mild reaction
since the discovery targeted by Tsuji and co-workers conditions (PCO =45 bar, temperature 60–808C), to
in 1964,[2] followed by the contribution of Heck of obtain dibutyl succinates with moderate selectivi-
1972.[3] Carbonylations allow one to directly convert ties.[7h] In 2001, Bianchini and co-workers reported
low value materials, like olefins or alkynes and a detailed study on the bis-alkoxycarbonylation of sty-
carbon monoxide, into a number of highly valuable rene, using pyridinimine ligands, Pd(TFA)2 as the pal-
carbonylated compounds, useful in synthetic organic ladium source and benzoquinone (BQ) as oxidant.
chemistry as well as pharmaceutical and medicinal However, only modest results in terms of conversion
chemistry.
and yield could be achieved under their conditions.[7k]
Succinic acid and its derivatives are particularly im- Regarding the asymmetric counterpart, in the litera-
portant compounds, as they find application in materi- ture two different main approaches have been report-
al science[4] and in the syntheses of inhibitors of ed. Consiglio[8b,c] and Chan,[8h] using several chiral di-
renin[5] and matrix metalloproteinase.[6] A particularly phoshine palladium complexes, obtained dimethyl
attractive method for the direct synthesis of succinic phenylsuccinate with high enantioselection, but
acid diesters from simple and readily available feed- modest conversion and selectivity, using BQ as oxi-
stocks consists in the Pd-catalyzed oxidative bis-al- dant under an elevated carbon monoxide pressure.[8c,h]
koxycarbonylation of olefins. Even though the overall On the other hand, Inomata and Huang used chiral
process has been widely recognized to be of high N,N and N,S ligands in combination with Pd[II]/Cu[I]
practical importance, only in recent times has it salts and oxygen.[8e,f,i] By running the bis-alkoxycarbo-
gained major attention both in the achiral[7] and asym- nylation of different styrenes with high catalyst load-
metric versions.[8] After the pioneering work by ings under mild reaction conditions, moderate enan-
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Francesco Fini et al.
Scheme 1. N,N-Diaryl DAB ligands 1a–i.
tioinductions and yields were achieved.[8e,f,i] Although ligand 1d (Table 1, entry 5). On the other hand, using
these contributions are important, an efficient meth- the ortho-disubstituted-diaryl DAB ligands 1e and 1f,
odology for synthesizing succinic diesters with high bearing bulky isopropyl groups (1e) or methyl groups
conversion and selectivity, under mild reaction condi- (1f) in the ortho positions of the aromatic rings
tions has not been reported yet.
(Scheme 1), good conversions were attained (Table 1,
In the last years, our group has extensively studied entries 6 and 7), albeit the desired compound 3a was
the catalytic behavior of Pd(II) complexes containing obtained in a mixture with 4-(4-hydroxyphenyl) 1-
aryl a-diimine (N,N-diaryl-diazabutadiene, DAB) li- methyl 2-phenylsuccinate 4a as by-product in differ-
gands. Particularly interesting results have been ob- ent proportions. Formation of 4a was clearly due to
tained in the CO/styrene copolymerization reaction, the participation of hydroquinone (formed by reduc-
leading to a copolymer of high tacticity with good tion of BQ under the reaction conditions) as nucleo-
yields.[9] Despite their stability, accessibility,[10] and ef- phile in the carbonylation reaction. Passing from
ficacy as ligands to Pd, DAB ligands have not been ligand 1f to 1g and 1h, bearing diverse diimine back-
used so far in the bis-alkoxycarbonylation of olefins. bones, no beneficial effects were noted (Table 1, com-
Considering our previous know-how, and the quite pare entry 7 with entries 8 and 9). On the other hand,
close structural analogy between DAB and the bisox- when the amount of benzoquinone was increased (up
azoline ligands employed by Inomata and co-work- to 1.5 equiv.), a complete conversion was achieved,
ers,[8f,11] we undertook an extensive study on the use with a 3a:4a ratio of 87:13, with the ortho-dimethyl
of these proficient ligands in the palladium-catalyzed disubstituted ligand 1f (Table 1 entry 10). The effi-
oxidative carbonylation of olefins to succinic acid die- ciency of the Pd(TFA)2/1f catalyst was assessed by
sters.
performing the bis-alkoxycarbonylation reaction with
a significantly lower catalyst loading. With 0.5 mol%
of catalyst, a complete conversion was reached after
42 h reaction time, although the amount of 4a in-
creased (up to 65:35; Table 1, entry 11). With
Results and Discussion
Our initial experiments on the use of DAB ligands 0.1 mol% of catalyst, a 30% conversion of styrene
for the oxidative bis-alkoxycarbonylation of olefins was observed after 42 h (Table 1, entry 12).
were carried out on styrene using diaryl-DAB ligands
With these preliminary data in hand, an extensive
1a–h (Scheme 1) and Pd(TFA)2 as palladium source, optimization study of the reaction conditions was car-
in a 1:1 mixture of methanol/THF as reaction medium ried out, aimed, in particular, at improving the selec-
and BQ as oxidizing agent.[12] Reactions were con- tivity of the process toward the desired product 3a.
ducted under particularly mild conditions, under 4 bar Full details of this study are given in the Supporting
of CO at 208C (Table 1).
Information (Table S1), while representative results
While no reaction took place in the absence of li- are shown in Table 2.
gands, (Table 1, entry 1), the use of ligands 1a–c, bear-
From this investigation, a beneficial effect of in-
ing unsubstituted or para-substituted aryl groups, creasing the MeOH/THF ratio on selectivity
(Scheme 1) did promote the formation of dimethyl emerged: in fact, using 1f as ligand in a 7:1 MeOH/
succinate 3a, with modest but encouraging conver- THF mixture as reaction medium, the 3a:4a ratio was
sions (Table 1, entries 2–4). Similar results were ob- 75:25 (Table 2, entry 1; to be compared with entry 11
tained with the mono-ortho-tert-butyl substituted of Table 1). Moreover, the use of p-toluenesulphonic
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Selective Aryl a-Diimine/Palladium-Catalyzed Bis-Alkoxycarbonylation
Table 1. Bis-methoxycarbonylation reaction of styrene catalyzed by Pd(TFA)2 with ligands 1a–h. Effect of the ligand and
BQ.
Entry[a]
Ligand 1a–h
Time [h]
Conversion [%][b]
3a:4a ratio[b]
1
2
3
4
5
6
7
8
–
42
42
170
170
72
42
72
48
72
21
42
42
<5
50
40
25
40
70
90
40
85
ND
50:0
40:0
25:0
1a
1b
1c
1d
1e
1f
1g
1h
1f
1f
1f
40:0
60:10
75:15
40:0
65:20
87:13
65:35
28:2
9
10[c]
11[d]
12[e]
ꢀ 98
ꢀ 98
30
[a]
Reaction performed in autoclave at PCO =4 bar, with styrene (2 mmol scale), 2 mol% of Pd(TFA)2, 2.2 mol% of 1a–h and
1 equiv. of BQ with THF/MeOH 1:1 (0.5M) as reaction medium.
Determined by direct H NMR analysis of a sample of the reaction mixture.
Reaction performed with 1.5 equiv. of BQ.
Reaction performed with 0.5 mol% of Pd(TFA)2, 0.55 mol% of 1f and 1.5 equiv. of BQ.
Reaction performed with 0.1 mol% of Pd(TFA)2, 0.11 mol% of 1f and 1.5 equiv. of BQ.
[b]
[c]
[d]
[e]
1
Table 2. Representative results on the Pd(TFA)2/DAB-catalyzed bis-methoxycarbonylation of styrene carried out under dif-
ferent reaction conditions.
Entry[a]
Ligand/amount of Pd(TFA)2
Additive
Time [h]
Conversion [%][b]
3a:4a ratio[b]
1
2
3
4
1f/0.5 mol%
1f/0.5 mol%
1f/0.1 mol%
1f/0.1 mol%
1i/0.5 mol%
1i/0.1 mol%
1i/0.5 mol%
1i/0.1 mol%
–
42
42
42
42
66
66
66
66
ꢀ 98
90
25
75:25
80:10
25:0
65:10
95:5
45:0
80:5
25:0
p-TSA (2.0 mol%)
–
p-TSA (0.5 mol%)
p-TSA (2.0 mol%)
p-TSA (0.5 mol%)
p-TSA (2.0 mol%)
p-TSA (0.5 mol%)
75
5
ꢀ 98
6
45
7[c]
8[c]
85
25
[a]
Reaction performed in an autoclave at PCO of 4 bar, with styrene 2a (2 mmol scale), 0.5 or 0.1 mol% of Pd(TFA)2, 0.55 or
0.11 mol% of 1f or 1i, and 1.5 equiv. of BQ, with MeOH/THF 7:1 (0.5M) as the reaction medium.
Determined by direct H NMR analysis on a sample of the reaction mixture.
[b]
[c]
1
Reaction performed in a Schlenk tube at atmospheric pressure of CO.
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Table 3. Scope of the bis-alkoxycarbonylation reaction of
aryl and alkyl olefins.
Table 3. (Continued)
Entry[a] 2a–l
3a–n
Yield
[%][b]
12[f]
13[g]
14[h]
77
53[e] (95)
Entry[a] 2a–l
3a–n
Yield
[%][b]
92
94
1
2
91
97
15[h]
[a]
Reactions performed in autoclave at a PCO of 4 bar, with
olefins 2a–l (2 mmol scale), 0.5 mol% of Pd(TFA)2,
0.55 mol% of 1i, 2 mol% of p-TSA and 1.5 equiv. of BQ,
in 7:1 MeOH/THF (0.5M) as the reaction medium, for
66 h.
Isolated yields after column chromatography.
Reaction performed with 1 mol% catalyst loading and
2 mol% of p-TSA in 7:1 MeOH/THF (0.25M) as the re-
action medium.
3c
4
88[d]
90[d]
[b]
[c]
[d]
[e]
The presence of a small amount of by-products 4 (less
than 7%) in the crude mixture was detected by
1H NMR.
5
6
96
91
Conversion of the a-olefins and, in parenthesis, isolated
yields of the converted product are reported.
Reaction performed with 1 mol% catalyst loading.
Reaction performed with 2 mol% catalyst loading.
Reaction performed with 2 mol% catalyst loading, using
i-PrOH or BnOH in place of methanol.
[f]
[g]
[h]
7
8
9
75[e] (94)
45[e] (91)
85
acid (p-TSA) as additive (in a 4 to 5 molar ratio with
palladium) caused a significant improvement in the
efficiency of the process (Table 2, entries 2 and 4): in
particular, lowering the catalyst loading down to
0.1 mol%, a catalytic TON of 750 and a TOF of
18 hÀ1 were achieved, with a 3a:4a ratio of 65:10
(compare entry 4 in Table 2 with entry 12 in Table 1).
Continuing the process of optimization, we also tested
the new ligand bis(9-anthryl)-2,3-dimethyl-1,4-diaza-
butadiene 1i recently synthesized by our group for the
Pd-catalyzed CO/styrene copolymerization.[9a] This
ligand led to the best results in terms of styrene con-
version (>98%) and selectivity toward 3a (95%), as
shown in Table 2, entry 5.[13] Remarkably, the catalyst
Pd(TFA)2/1i was active even at atmospheric pressure
of CO (Table 2, entries 7 and 8).
10[f]
11[f]
87[d]
92
We next investigated the generality of this new effi-
cient and selective catalytic system in the bis-alkoxy-
carbonylation reaction with different vinylarenes and
aliphatic olefins (Table 3).
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Selective Aryl a-Diimine/Palladium-Catalyzed Bis-Alkoxycarbonylation
The succinic acid methyl esters 3a–l were obtained
in good to excellent yields, regardless of the different
electronic character of the substituents on the aromat-
ic ring (Table 3, entries 1–10). The best isolated yield
(97%) was achieved using para-methylstyrene as sub-
strate (Table 3, entry 2). While with olefin 2c, bearing
a strong p-donating group, such as p-OMe, a slight in-
crease of catalyst loading under more diluted condi-
tions was needed to minimize the formation of by-
product 4c, obtaining 3c in 88% yield (Table 3,
entry 3). p-Br, p-Cl, and m-CF3 substituents were
quite well tolerated in the reaction, with the corre-
sponding esters 3e, 3f, and 3i being obtained with ex-
cellent yields (Table 3, entries 5, 6 and 9, respective-
ly). However, vinylarenes 2g and 2h, bearing o-Cl and
o-Br substituents, respectively, were less reactive, and
incomplete conversion was observed, even though the
selectivity toward diesters 3g and 3h was still high
(Table 3, entries 7 and 8). 2-Vinylnaphtalene 2j and
aliphatic olefins, such as 1-heptene 2k and 1-(but-3-
enyl)benzene 2l, were in general less reactive than
styrenes, and a slight increase of catalyst loading (up
to 1 mol%) was necessary to achieve satisfactory re-
sults in terms of isolated yield and selectivity in the
corresponding succinic diesters 3j–l (Table 3, en-
tries 10–12). Even with an aliphatic olefin hindered in
the alpha position,[14] such as 3,3-dimethyl-1-butene
2m, the carbonylated product 3m was obtained with
95% yield over a converted starting material of 53%
(Table 3, entry 13), with 2 mol% of catalyst loading.
A survey of different alcohols as nucleophiles in place
of methanol was made to prove the broadness of the
methodology and to synthesize different products
with orthogonal cleavable isopropyl and benzyl ester
groups (3n and 3o), very useful in synthetic organic
and medicinal chemistry (Table 3 entries 13 and 14).
Isopropyl alcohol and benzyl alcohol were reactive
enough to cause complete styrene conversion, even
though with a higher catalyst loading [2 mol% of
Pd(TFA)2/1i; Table 3, entries 13 and 14].[15]
Scheme 2. Bis-alkoxycarbonylation reaction with 1,2-disub-
stituted olefins 2n and 2o.
Scheme 3. Proposed catalytic cycle.
Regarding internal olefins, while no reaction was
observed using the initial reaction conditions reported
in Table 1, and ligands 1a and 1b, the carbonylation
According to the above results and literature
performed with Pd(TFA)2/1i (2 mol%) allowed a com- data,[7k,9,11] we can propose the reaction mechanism
plete conversion of cis- and trans-b-methylstyrene shown in Scheme 3. The first step of the process is the
(Scheme 2).
formation of the active species A from the reaction
The resulting products 3p and 3q were obtained in between Pd(TFA)2, the DAB ligand and the alco-
good isolated yields of 92% and 87% respectively, hol.[18] Insertion of CO leads to the alkoxycarbonyl-
with total diastereoselectivity (Scheme 2). The geome- palladium complex B, which, after insertion of the
try of compounds 3p and 3q comes from a syn overall alkene 2, affords the 5-membered palladacycle inter-
addition of the carboxyl moieties to the olefin.[16] This mediate C,[11] however formation of an h3-allylic inter-
process, in agreement with a generally accepted mediate in equilibrium with C cannot be ruled out.[9]
mechanism, passes through a concerted syn addition In any case, further CO insertion to give complex D,
of the Pd-carbonyl fragment of the catalyst to the followed by nucleophilic displacement by the alcohol,
olefin double bond, via a four-membered transition leads to the final product 3 and palladium hydride
state.[11,17]
complex E. Finally, the intervention of benzoquinone
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regenerates the active species A thus closing the cata- CO at 208C). Variously substituted aryl a-diimine li-
lytic cycle.[12]
gands have been used for the first time in this kind of
The main parameters that influence our bis-alkoxy- reaction, together with Pd(TFA)2 as palladium source,
carbonylation method are: the type of ligand, the alcohols as nucleophiles and 1,4-benzoquinone as oxi-
presence of p-TSA and the ROH/THF ratio. While dant. In particular, the 9-anthryl ligand 1i gave the
the last parameter mainly affects the ratio of com- best results in terms of substrate conversion and prod-
pounds 3/4, the roles played by the p-TSA and the uct yield, with low catalyst loading (0.5–2 mol%). The
ligand are more complex. First of all, the sulphonic optimized reaction conditions could be successfully
acid has clearly two effects: it increases the 3/4 ratio applied to both aromatic and aliphatic olefins, with
and enhances the catalytic efficiency (TON and different alcohols as nucleophiles, including the steri-
TOF). In particular, it appears that p-TSA decreases cally hindered i-PrOH. The enantioselective version
the amount of the phenate anion in equilibrium with of our bis-alkoxycarbonylation is currently under in-
hydroquinone, suppressing the formation of product vestigation in our laboratories.
4. Moreover, as reported by Bianchini et al.,[7k] the
acid stabilizes the intermediate complex
E
(Scheme 3) and improves the oxidizing ability of BQ, Experimental Section
avoiding the formation of palladium black.[7k] Regard-
ing the ligand, catalytic species generated from li- General Methods and Materials
gands bearing ortho-disubstituted aryl rings, such as
All reactions were carried out under nitrogen atmosphere
1f and 1i, appear to be more active than the other
ones. This is probably due to the particular conforma-
tion of the in situ formed complexes. In fact, with li-
gands 1f and 1i, strong steric interactions between the
substituents of the diimine backbones and the phenyl
rings constrain the aryls to arrange almost perpendic-
ularly with respect to the palladium mean coordina-
tion plane.[9] This conformation affects the coordina-
tion of the aromatic olefin making possible a p stack-
ing interaction in the olefin insertion transition states
that could be the origin for the high productivity
found both in the CO/vinylarene copolymerization[9]
and in the bis-alkoxycarbonylation reaction reported
here. With the ortho-disubstituted aryl ligand 1e the
reaction still occurs but the conversion was not satis-
factory (70%, Table 1 entry 6) probably due to the
highly bulky isopropyl groups on the aryls which
cause a difficult access of the olefin and CO to the
catalytic center.[9] Conversely the methyl groups in
the Pd(TFA)2/1f catalyst have the exact size to pro-
mote the reaction to completion, but the selectivity
towards MeOH or HQ, to achieve 3:4 in good ratio,
is still lacking (Table 1 entry 7 and 10).[9] Finally the
complete conversion and selectivity observed in the
bis-alkoxycarbonylation reaction with Pd(TFA)2/1i
catalyst (Table 2, entry 5) can be ascribed to the pre-
cise steric hindrance of the anthryl moieties and to
a greater ability of complex D (Scheme 3) to undergo
alcoholysis by ROH rather than cleavage by hydro-
quinone.
with dry solvents under anhydrous conditions, in a stainless
steel autoclave, by using Schlenk techniques. Reactions were
1
monitored by H NMR taking a direct sample of the crude
mixture. 1H NMR and 13C NMR were recorded on a Brucker
Avance 200 spectrometer (1H: 200 MHz, 13C: 50 MHz),
using CDCl3 as solvent. Chemical shifts are reported in the
1
d scale relative to residual CHCl3 (7.26 ppm) for H NMR
and to the central line of CDCl3 (77.10 ppm) for 13C NMR.
13C NMR were recorded with 1H broadband decoupling.
The following abbreviations were used to explain the multi-
plicities: s=singlet, d=doublet, t=triplet, q=quartet,
hept=heptet, m=multiplet, dd=double doublets, br=
broad. Mass spectra were recorded on a LC-MS apparatus
Waters 2795, Micromass ZQ using electrospray (ES+) ioni-
zation techniques. Carbon monoxide (Cp grade 99.99%) was
supplied by Air Liquide, benzoquinone was purchased by
Sigma–Aldrich and was recrystallized from n-heptane/EtOH
mixture, olefins 2a–o were purchased from Sigma–Aldrich
or Alfa Aesar or TCI, filtered off a plug of neutral Al2O3
and used without further purification. Anhydrous THF was
distilled from sodium-benzophenone, and methanol was dis-
tilled from Mg(OMe)2. Pd(TFA)2 was weighed in an analyti-
cal balance without excluding moisture and air. All other
chemicals were purchased from Sigma–Aldrich and used
without further purification. Ligands 1a–h, used in the opti-
mization reaction were synthesized according to the previ-
ously reported procedure.[10] Ligand 1i was synthesized by
our group according to a previously reported procedure.[9a]
Compounds 3a–f, j, l were already known and the spectral
date are identical to the previously reported literature data
(see the Supporting Information for more details).[8i]
Typical Procedure for the Bis-alkoxycarbonylation
Reaction of Olefins
Conclusions
In a nitrogen-flushed Schlenk tube, equipped with a magnet-
ic stirring bar, Pd(TFA)2 (3.3 mg, 0.01 mmol) and THF
(0.5 mL) were added in sequence. After the mixture had
turned to a red/brown color (20 min), the ligand 1i (4.8 mg,
0.011 mmol) was added. The mixture was left stirring for
We have developed an efficient method for the Pd-
catalyzed bis-alkoxycarbonylation of olefins 2 to give
succinic diesters 3 in good yields and high selectivity,
under particularly mild reaction conditions (4 bar of 10 min, changing to a dark-green color. The formed catalyst
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Selective Aryl a-Diimine/Palladium-Catalyzed Bis-Alkoxycarbonylation
was injected in a nitrogen-flushed autoclave, equipped with
a magnetic stirring bar, containing benzoquinone (325 mg,
3 mmol) and p-TSA·H2O (7.6 mg, 0.04 mmol) in MeOH
(3.5 mL). After 10 min of stirring, the respective olefin 2a–o
(2 mmol) was added in one portion into the reaction mix-
ture. The autoclave was flushed three times with CO and
pressurized to 4 bar of carbon monoxide. The reaction mix-
ture was vigorously stirred at the room temperature (208C)
for 66 h. The autoclave was vented off, flushed with nitrogen
173.3, 51.9, 51.4, 51.3, 32.7, 27.9; ESI-MS: m/z=203 [M+
H]+.
Diisopropyl 2-phenylsuccinate (3n): Following the general
procedure, but performing the reaction with 2 mol% catalyst
loading [13.3 mg, 0.04 mmol of Pd(TFA)2 and 19.2 mg,
0.044 mmol of 1i] and using i-PrOH as the alcohol, com-
pound 3n was obtained as a colorless oil; yield: 92%.
1H NMR: d=7.26 (br s, 5H), 4.98 (hept, J=6.3 Hz, 1H),
4.97 (hept, J=6.2 Hz, 1H), 4.01 (dd, J=5.5, 10.2 Hz, 1H),
3.12 (dd, J=10.2, 16.7 Hz, 1H), 2.60 (dd, J=5.5, 16.7 Hz,
1H), 1.22 (d, J=6.3 Hz, 3H), 1.19 (d, J=6.2 Hz, 3H), 1.16
(d, J=6.2 Hz, 3H), 1.08 (d, J=6.3 Hz, 3H); 13C NMR: d=
172.4, 171.0, 138.0, 128.7, 127.7, 127.4, 68.4, 68.1, 47.5, 38.2,
21.7, 21.7, 21.4; ESI-MS: m/z=278 [M+H]+.
1
and the reaction mixture was directly analyzed by H NMR
to determine the conversion and the ratio of the products 3
and 4. The crude material was then dried under reduced
pressure and filtered through a plug of silica gel, washing
with CH2Cl2/Et2O 8:2 (25 mL) and finally the solution was
evaporated under vacuum. The product was eventually ob-
tained after column chromatography on silica gel (petrole-
um ether/CH2Cl2 50:50 then 30:70).
Dibenzyl 2-phenylsuccinate (3o): Following the general
procedure, but performing the reaction with 2 mol% catalyst
loading [13.3 mg, 0.04 mmol of Pd(TFA)2 and 19.2 mg,
0.044 mmol of 1i] and using BnOH as the alcohol, com-
pound 3o was obtained as a colorless oil; yield: 94%.
1H NMR: d=7.51–7.09 (m, 15H), 5.10 (br s, 4H), 4.18 (dd,
J=9.9, 5.5 Hz, 1H), 3.29 (dd, J=16.9, 10.0 Hz, 1H), 2.77
(dd, J=16.9, 5.5 Hz, 1H); 13C NMR: d=172.7, 171.3, 137.5,
135.8, 135.7, 128.9, 128.6, 128.50, 128.33, 128.28, 128.2, 127.9,
127.8, 66.8, 66.7, 47.4, 37.8; ESI-MS: m/z=375 [M+H]+.
(2R*,3R*)-Dimethyl 2-methyl-3-phenylsuccinate (3p):
Following the general procedure, but performing the reac-
tion with 2 mol% of catalyst loading [13.3 mg, 0.04 mmol of
Pd(TFA)2 and 19.2 mg, 0.044 mmol of 1i], compound 3p was
Dimethyl 2-(2-chlorophenyl)succinate (3g): Following the
general procedure, compound 3g was obtained as a pale
yellow oil; yield: 94% (over a conversion of 75% of 2-chlor-
ostyrene 2g, determined by 1H NMR analysis on a direct
1
sample of the reaction mixture). H NMR: d=7.47–7.13 (m,
4H), 4.60 (dd, J=9.8, 5.1 Hz, 1H), 3.67 (s, 3H), 3.66 (s,
3H), 3.13 (dd, J=17.0, 9.8 Hz, 1H), 2.65 (dd, J=17.0,
5.1 Hz, 1H); 13C NMR: d=172.9, 171.7, 135.6, 133.6, 130.0,
128.9, 128.8, 127.3, 52.4, 51.9, 44.0, 36.4; ESI-MS: m/z=257
[M+H]+.
Dimethyl 2-(2-bromophenyl)succinate (3h): Following the
general procedure, compound 3h was obtained as a pale
yellow oil; yield: 91% (over a conversion of 45% of 2-bro-
1
obtained as a pale yellow wax; yield: 92%. H NMR: d=
7.36–7.21 (m, 5H), 3.81 (d, J=10.9 Hz, 1H), 3.65 (s, 3H),
3.40 (s, 3H), 3.24 (dq, J=10.9, 6.8 Hz, 1H), 1.28 (d, J=
6.8 Hz, 3H); 13C NMR: d=174.3, 172.5, 136.6, 128.4, 128.1,
127.6, 54.6, 51.9, 51.3, 43.6, 16.2; ESI-MS: m/z=237 [M+
H]+.
(2S*,3R*)-Dimethyl 2-methyl-3-phenylsuccinate (3q): Fol-
lowing the general procedure, but performing the reaction
with 2 mol% of catalyst loading [13.3 mg, 0.04 mmol of
Pd(TFA)2 and 19.2 mg, 0.044 mmol of 1i], compound 3q was
obtained as a pale yellow oil; yield: 87%. 1H NMR: d=
7.44–7.25 (m, 5H), 3.81 (d, J=11.4 Hz, 1H), 3.77 (s, 3H),
3.67 (s, 3H), 3.21 (dq, J=11.3, 7.3 Hz, 1H), 0.99 (d, J=
7.3 Hz, 3H); 13C NMR: d=176.0, 173.6, 136.2, 128.8, 128.3,
127.7, 54.1, 52.0, 51.9, 42.2, 15.3; ESI-MS: m/z=237 [M+
H]+.
1
mostyrene 2h, determined by H NMR analysis on a direct
1
sample of the reaction mixture). H NMR: d=7.61–7.54 (m,
1H), 7.30–7.21 (m, 2H), 7.18–7.07 (m, 1H), 4.63 (dd, J=
10.0, 4.9 Hz, 1H), 3.66 (s, 3H), 3.64 (s, 3H), 3.12 (dd, J=
17.0, 10.0 Hz, 1H), 2.68 (dd, J=17.0, 5.0 Hz, 1H);
13C NMR: d=172.9, 171.7, 137.4, 133.4, 129.1, 128.8, 128.0,
124.3, 52.5, 52.0, 46.4, 36.7; ESI-MS: m/z=301 [M+H]+.
Dimethyl 2-(3-(trifluoromethyl)phenyl)succinate (3i): Fol-
lowing the general procedure, compound 3i was obtained as
1
a colorless oil; yield: 85%. H NMR: d=7.59–7.40 (m, 4H),
4.15 (dd, J=5.5 Hz, 9.8 Hz, 1H), 3.66 (s, 3H), 3.64 (s, 3H),
3.21 (dd, J=9.7, 17.0 Hz, 1H), 3.21 (dd, J=5.5, 17.0 Hz,
1H); 13C NMR: d=172.8, 171.6, 138.7, 131.30 (q, J=
1.1 Hz), 131.28 (q, J=32.4 Hz), 129.5, 124.74 (q, J=3.7 Hz),
124.69 (q, J=3.7 Hz), 124.0 (q, J=272.4 Hz), 52.6, 52.0, 46.9,
37.4; ESI-MS: m/z=291 [M+H]+.
Dimethyl 2-pentylsuccinate (3k): Following the general
procedure, but performing the reaction with 1 mol% catalyst
loading [6.6 mg, 0.02 mmol of Pd(TFA)2 and 9.6 mg,
0.022 mmol of 1i] compound 3k was obtained as a colorless
oil; yield: 92%. 1H NMR: d=3.70 (s, 3H), 3.68 (s, 3H),
2.93–2.64 (m, 2H), 2.44 (dd, J=15.9, 4.6 Hz, 1H), 1.72–1.43
(m, 2H) 1.39–1.13 (m, 6H), 0.97–0.79 (m, 3H); 13C NMR:
d=175.7, 172.7, 51.8, 51.7, 41.1, 35.7, 31.8, 31.4, 26.5, 22.3,
13.9; ESI-MS: m/z=217 [M+H]+.
Acknowledgements
This work was supported by Ministero dell’Universitꢀ e della
Ricerca (PRIN n. 2008A7P7YJ).
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solution of Pd(TFA)2 and benzoquinone, to avoid a rel-
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8
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Selective Aryl a-Diimine/Palladium-Catalyzed Bis-Alkoxy-
carbonylation of Olefins for the Synthesis of Substituted
Succinic Diesters
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Adv. Synth. Catal. 2014, 356, 1 – 9
Francesco Fini,* Michela Beltrani, Raffaella Mancuso,
Bartolo Gabriele, Carla Carfagna*
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These are not the final page numbers!